Daoud Georges, Simoneau Lucie, Masse André, Rassart Eric, Lafond Julie
Laboratoire de Physiologie materno-fonetale, Département des Sciences Biologiques, Université du Québec à Montréal, Succursale Centre-ville, Montréal, Québec, Canada H3C 3P8.
Biochim Biophys Acta. 2005 Feb 21;1687(1-3):181-94. doi: 10.1016/j.bbalip.2004.11.017.
Throughout gestation, fetal growth depends, in part, on placental transfer of maternal essential fatty acid (EFA) and long-chain polyunsaturated fatty acid. All fatty acid (FA) can cross lipid bilayer by simple diffusion, such as those in the syncytiotrophoblasts, the multinucleated, terminally differentiated trophoblast cells. The trophoblasts differentiation process is accompanied by an increase of human chorionic gonadotropin (hCG) secretion and an inhibition of Human Achaete-Scute Homologue-2 expression (Hash-2). Furthermore, a number of FA-binding proteins (FABPs) have been identified in membrane and cytoplasm of mammalian cells, which are thought to facilitate the transfer of FA across membranes and their intracellular channeling. Thus, the aim of this study was to investigate the implication of cFABPs in linoleic acid (LA) uptake by human trophoblast cells according to differentiation. Moreover, since peroxisome proliferator-activated receptor (PPARs) regulate the expression of cFABP and play an important role in trophoblast cells differentiation, the effects of PPARs ligands are verified on cFABP expression and differentiation. Herein, we reported the increase of the expression of liver and heart FABP (L- and H-FABP) upon differentiation of trophoblast cells, an inhibition of PPAR alpha and beta, while PPAR gamma levels remains unchanged. The nonselective peroxisome-proliferating agents, bezafibrate and LA, impaired trophoblast differentiation, and reduced L- and H-FABP expression. Furthermore, cobalt, a chemical agent known to mimic hypoxia, inhibits trophoblast cells differentiation and diminishes H-, L-FABP and PPARs expression. Finally, both treatments show no influence on LA uptake by trophoblast cells. In conclusion, this study showed that there is no correlation between the expression of H- and L-FABP and LA uptake by trophoblast cells and that bezafibrate and LA greatly impaired trophoblast cells differentiation.
在整个妊娠期，胎儿的生长部分依赖于母体必需脂肪酸（EFA）和长链多不饱和脂肪酸的胎盘转运。所有脂肪酸（FA）都能通过简单扩散穿过脂质双层，比如合体滋养层细胞（多核的终末分化滋养层细胞）中的脂肪酸。滋养层细胞的分化过程伴随着人绒毛膜促性腺激素（hCG）分泌增加以及人无翅型MMTV整合位点家族成员2（Hash-2）表达受到抑制。此外，在哺乳动物细胞的细胞膜和细胞质中已鉴定出多种脂肪酸结合蛋白（FABP），它们被认为有助于脂肪酸跨膜转运及其细胞内通道运输。因此，本研究的目的是根据分化情况研究细胞质脂肪酸结合蛋白（cFABP）在人滋养层细胞摄取亚油酸（LA）中的作用。此外，由于过氧化物酶体增殖物激活受体（PPAR）调节cFABP的表达并在滋养层细胞分化中起重要作用，因此验证了PPAR配体对cFABP表达和分化的影响。在此，我们报道了滋养层细胞分化后肝脏和心脏FABP（L-FABP和H-FABP）表达增加，PPARα和β受到抑制，而PPARγ水平保持不变。非选择性过氧化物酶体增殖剂苯扎贝特和LA损害了滋养层细胞分化，并降低了L-FABP和H-FABP的表达。此外，钴（一种已知可模拟缺氧的化学试剂）抑制滋养层细胞分化并降低H-FABP、L-FABP和PPAR的表达。最后，两种处理对滋养层细胞摄取LA均无影响。总之，本研究表明H-FABP和L-FABP的表达与滋养层细胞摄取LA之间没有相关性，并且苯扎贝特和LA极大地损害了滋养层细胞分化。
